Angiotensin II receptor subtypes in the skeletal muscle vasculature of patients with severe congestive heart failure

Background-Vascular remodeling occurs in the skeletal muscle of patients wi th severe congestive heart failure (CHF); this remodeling is mediated in pa rt by increased activity of the renin-angiotensin system. Animal models sug gest that in the vasculature, angiotensin II receptor type 2 (AT2-R) expres sion may be upregulated in pathological states associated with vascular rem odeling. The therapeutic effects of an ATL-R antagonist may, therefore, be in part due to increased plasma angiotensin II levels, which stimulate AT2- R. However, whether AT2-R is expressed in the skeletal muscle vasculature o f patients with severe CHF is unknown. Methods and Results-The steady-state transcript levels of the AT1-R and AT2 -R genes were analyzed by reverse transcription-polymerase chain reaction i n RNA samples prepared from the skeletal muscle of 12 patients with severe CHF (VO2<10 mL.kg(-1).min(-1)) and 5 age-matched healthy subjects who under went vastus lateralis biopsies. Human fetal skeletal muscle RNA served as a positive control for the expression of ATI-R and AT2-R gene transcripts; T ranscripts from the ATI-R gene were detected readily in all samples. In con trast, transcripts from the AT2-R gene were only detected in fetal skeletal muscle samples and could not be detected in the skeletal muscle vasculatur e of healthy subjects or that of CHF patients, who were treated with either angiotensin-converting enzyme inhibitors or AT1-R antagonists. Conclusions-The AT2-R gene is not expressed in the skeletal muscle of patie nts with CHF, In the absence of detectable AT2-R gene transcripts, the AT2- R pathway is unlikely to contribute to the effects of ATI-R antagonists on the skeletal muscle vasculature in patients with severe CHF.